Posted Mon, Aug, 17,2015
This author interview is by Dr Brendan D. Stamper, of Pacific University. Dr Stamper's full paper, p53 is a key regulator in differentiating gene expression following exposure to acetaminophen and its less hepatotoxic regioisomer both in vitro and in vivo, is available for download in Gene Regulation and Systems Biology.
Please summarize for readers the content of your article
The work outlined in this manuscript provides a comprehensive analysis of different transcriptomic data derived from multiple model systems treated with toxicologically relevant doses of acetaminophen (APAP). The results from these studies were refined by employing a structure-toxicity relationship with the meta-isomer of APAP, acetyl-m-aminophenol (AMAP). In the end, p53 signaling was identified as the most robust pathway contributing to APAP-induced toxicity at the transcriptomic level. These transcriptomic changes were subsequently verified by protein-level analyses.
How did you come to be involved in your area of study?
I have always been fascinated by how subtle changes in a chemical’s structure can have a significant impact on biologic activity. As a graduate student in the University of Washington’s medicinal chemistry program, I was able to apply genomic technologies to better characterize toxicologic changes associated with subtle structural modifications. Studying the structure-toxicity relationship between APAP and AMAP was and continues to be the main focus of my research as an Assistant Professor at Pacific University.
What was previously known about the topic of your article?
A number of toxicogenomic studies have identified transcriptomic profiles and patterns of expression related to APAP-induced toxicity. These studies have been incredibly valuable in identifying a large number of potential biomarkers associated with APAP overdose. By using AMAP as a comparative tool, this work was capable of narrowing down this pool of biomarkers to a shorter and more robust list of consistently altered transcripts associated with p53 signaling.
How has your work in this area advanced understanding of the topic?
This work provides added leverage for continued efforts towards understanding the role of p53 signaling in APAP-induced toxicity.
What do you regard as being the most important aspect of the results reported in the article?
The most important result from this work is the fact that APAP-induced perturbations to p53 signaling were consistent in both an in vitro and in vivo model, as well as across multiple microarray platforms. This evidence suggests that p53 signaling is a consistent mechanistic contributor during APAP overdose situations. In addition, this manuscript was the first to report APAP-specific induction of p53 phosphorylation at serine-392.
Posted in: Authors
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